Cancer is the leading cause of death. Treatment currently performed for cancer is mainly surgical therapy, which can be combined with radiation therapy or chemotherapy. In spite of development of new surgical methods and discovery of new anti-cancer agents in recent years, treatment results of cancers are not greatly improved at present except for some cancers. Through a recent progress of molecular biology and cancer immunology, antibodies that are specifically reactive with cancers, cancer antigens recognized by cytotoxic T cells, as well as the genes encoding the cancer antigens, have been identified, and expectations for specific immunotherapies targeting cancer antigens have been raised (Tsuyoshi AKIYOSHI, “Gan To Kagaku-Ryoho (Cancer and Chemotherapy),” 1997, vol. 24, pp. 551-519 (Jp) (Cancer and Chemotherapy Publishers, Inc., Japan)).
In cancer treatment methods, in order to reduce side effects, it is desirable for peptides, polypeptides, or proteins recognized as cancer antigens to be absent in almost all normal cells but specifically present in cancer cells. In 1991, Boon et al of the Ludwig Institute in Belgium isolated the human melanoma antigen MAGE 1 recognized by CD8-positive T cells by the cDNA-expression cloning method using an autologous cancer cell line and cancer-reactive T cells (Bruggen P. et al., Science, 254:1643-1647 (1991)). Thereafter, the SEREX (serological identification of antigens by recombinant expression cloning) method was reported, wherein tumor antigens recognized by antibodies produced through response to an autologous cancer in the body of a patient with cancer can be identified using the gene-expression cloning technique (Proc. Natl. Acad. Sci. USA, 92:11810-11813 (1995); and U.S. Pat. No. 5,698,396). By the SEREX method, some cancer antigens, which are not substantially expressed in normal cells but are specifically expressed in cancer cells, were isolated (Int. J. Cancer, 72: 965-971 (1997); Cancer Res., 58: 1034-1041 (1998); Int. J. Cancer, 29: 652-658 (1998); Int. J. Oncol., 14: 703-708 (1999); Cancer Res., 56: 4766-4772 (1996); and Hum. Mol. Genet 6: 33-39, 1997). Further, clinical trials of cell therapies using immunocytes that specifically react with cancer antigens, which are some of the isolated cancer antigens, and cancer-specific immunotherapies using vaccines comprising cancer antigens or the like have been conducted.
Meanwhile, in recent years, a variety of antibody medicines for cancer treatment that target antigen proteins on cancer cells have come into existence. Such medicines used as cancer-specific therapeutic agents exhibit drug efficacy to a certain extent, and thus they have been gaining attention. However, most of target antigen proteins are also expressed on normal cells. As a result of antibody administration, not only cancer cells, but also normal cells, on which a target antigen has been expressed can be damaged, thereby causing a side (or adverse) effect, which becomes problematic. Hence, it is expected that, if it becomes possible to identify cancer antigens that are specifically expressed on the surface of a cancer cell and to use antibodies targeting such antigens as medicaments, then treatment with antibody medicines that cause fewer side effects could be realized.
Cytoplasmic- and proliferation-associated protein 1 (CAPRIN-1) is an intracellular protein that is expressed when normal cells in resting phase are activated or undergo cell division. CAPRIN-1 is also known to be involved in the regulation of the transport and translation of mRNAs through formation of ctytoplasmic stress granules with RNA in a cell. CAPRIN-1 has different names, such as GPI-anchored membrane protein 1 and membrane component surface marker 1 protein (M11S1), as if this protein is known to be a membrane protein. These different names are derived from the report (J. Biol. Chem., 270: 20717-20723, 1995) that the gene sequence of CAPRIN-1 originally has a GPI-binding region and CAPRIN-1 is a membrane protein expressed in colon cancer cells. It was later reported that the CAPRIN-1 gene sequence described in said report was not correct; i.e., a frame shift took place by deletion of a single nucleotide from the CAPRIN-1 gene sequence currently registered with GenBank or the like, so that 80 amino acids were deleted from the C-terminus and the resulting artifact (74 amino acids) was the GPI binding portion in the report; and another error was also present on the 5′ side of the gene sequence, thereby resulting in deletion of 53 amino acids from the N-terminus (J. Immunol., 172: 2389-2400, 2004). Further, it has been reported that the protein encoded by the CAPRIN-1 gene sequence currently registered with GenBank or the like was not a cell membrane protein (J. Immunol., 172: 2389-2400, 2004).
In addition, based on the report of J. Biol. Chem., 270: 20717-20723, 1995 that CAPRIN-1 is a cell membrane protein, US2008/0075722 and WO2005/100998 disclose that CAPRIN-1 under the name of M11S1 can be used for cancer therapy as a target of antibody medicines for cancer therapy and as one of cell membrane proteins; however, the Examples contain no description of the cancer therapy using an antibody against the protein. However, as reported in J. Immunol., 172: 2389-2400, 2004, it was a common belief, from the time of filing US2008/0075722 up to now, that CAPRIN-1 is not expressed on the surface of a cell, and thus, it is obvious that the contents of US2008/0075722 and WO2005/100998 based only on misinformation that CAPRIN-1 is a cell membrane protein should not be understood as common technical knowledge of persons skilled in the art.